REB investigators evaluate the risks of multiple cancers following all cancers using the Surveillance Epidemiology and End Results Program cancer registry database including more than 2 million cancer survivors diagnosed from 1973 to 2008. Interesting findings from the 2006 Multiple Primary Monograph have been followed up with individual studies evaluating risk of radiation-related and chemotherapy-related second cancers. Particular studies of interest include of survivors of breast cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, retinoblastoma, and childhood cancers. In 2012 the first estimates of the proportion of second cancers related to radiotherapy were published. Cancer Following Radiotherapy for Benign Gynecologic Disorders - Cancer mortality following radiation treatment for benign gynecologic conditions in a cohort of nearly 15,000 women with individual radiation dose data is being updated to evaluate solid tumor and leukemia risk. Results were submitted for publication in 2012. Childhood Cancer Survivor Study - In a cohort of 14,000 5-year survivors of childhood cancer we performed nested case-control studies of second primary cancers of the breast, thyroid gland, salivary gland, bone, soft tissue and skin to evaluate the relationship between radiation and chemotherapy and risk of these cancers. A novel finding was that thyroid cancer risk was related to prior treatment with alkylating agents among patients exposed to radiation less than 20 Gy to the thyroid. New analyses of second breast cancers in relation to prior cancer treatment and potential effect modifiers has been initiated. The CCSS also is a unique resource and a rare opportunity in which to examine the potential for gene-radiation interaction. Particularly noteworthy are the availability of biospecimens, high quality information on doses of radiation and chemotherapy, and the young age at exposure of the cohort. We are currently performing a genome wide association study of subsequent neoplasms within this cohort (10597). Cancer Risk in Peptic Ulcer Patients - A of cohort of 2000 irradiated peptic ulcer patients is being compared to 2000 non-irradiated peptic ulcer patients to refine the dose-related risk for all cancers and cardiac disease and model the uncertainty in the dose estimates for these outcomes. Proton and intensity-modulated radiation therapy have the potential to deliver maximal doses to the tumor while minimizing dose to the surrounding tissues which may cause second cancers. Feasibility work in SEER-Medicare and local cancer registries is in progress. RF Analysis of Hematopoietic Malignancies in Various Radiotherapeutically Irradiated Cohorts - Parallel analysis using a variety of mathematical and statistical models of cancer risks associated with ionizing radiation exposure in the Japanese atomic bomb survivors and in therapeutically irradiated groups. Endpoints include all hematologic cancers, specifically leukemia (including chronic lymphocytc leukemia (CLL)), Hodgkins disease, non-Hodgkins lymphoma (NHL), and multiple myeloma. The models take account of cell repopulation and redistribution as a result of internal and external radiation exposure (including brachytherapy), and also factors such as age at exposure and attained age. Radiation Dose-Response and Second Primary Cancers of Stomach, Esophagus, and Pancreas - An international study of second primary gastrointestinal (GI stomach cancer, pancreatic cancer, and esophageal cancer) cancers is being conducted among survivors of Hodgkin lymphoma testis cancer, breast and cervical cancer to provide new data on radiation dose and subsequent risk of GI cancer. Findings to date have demonstrated a dose-related increased risk of esophageal cancer following breast cancer. Analyses of GI malignancy risk after HL and testis and cervical cancers as well as related dosimetry methods projects are in progress. Risk Factors for Second Cancers in the Cohort Consortium - The feasibility of studying second cancers in the NCI Cohort Consortium is being assessed. Second Cancers after Breast Cancer in Kaiser - The etiology of contralateral breast is probably related to treatment, genetic and lifestyle risk factors. We are exploring the feasibility of studying treatment and modifiable lifestyle risk factors for contralateral breast cancer in three different cohorts. Second Cancers Following Retinoblastoma - A cohort of 1,850 Retinoblastoma survivors continues to be monitored for the incidence and mortality of all second primary cancers, primarily of the bone, soft tissue, and melanoma in relation to past radiotherapy and chemotherapy. Studies of RB1 mutations and second cancer risks are in progress.